This proposed study is a competing renewal of a study on the nutritional status of HIV-positive and HIV-negative injection drug users (IDU) (NIDA-DA10252). Results from the first year of this 2.5 year grant indicate that serum antioxidant vitamins were similar between HIV-positive and HIV-negative IDUs. However, those HIV-positive participants on antiretroviral combination therapies (ART) including a protease inhibitor (PI) had significantly higher mean serum levels of several antioxidant vitamins compared to both HIV-negatives and HIV-positives not taking PI's. This difference was not explained by differences in dietary intake or supplement use. These results suggest that oxidative stress, as measured by serum antioxidants, may be reduced in patients taking PI's; however, this requires further investigation. Specifically, we would like to examine the associations between oxidative stress and serum antioxidant levels among HIV-negative IDUs and HIV-positive IDUs on various ART regimens. We will also examine the effect of oxidative stress and serum antioxidant levels on HIV disease progression. Furthermore, we have the opportunity to characterize a group of more active IDUs, many of whom are not on ART, with respect to oxidative stress and antioxidant status. The proposed renewal will build on the existing study (TANG - The ALIVE Nutrition Group) and the infrastructure of the ongoing ALIVE study (NIDA-DA04334). In addition to the subjects already enrolled in TANG (n=398), we plan to enroll 52 additional HIV-positive ALIVE participants to increase the sample size of each ARV therapy group to 50; 100 HIV-positive subjects who report injecting drugs at least 3 times a week, who have recently been recruited into the ALIVE study; and 30 HIV negative never-drug using volunteers from the community. Study participants will undergo dietary intake interviews, body composition measurements, and venipuncture for serum measures of oxidative stress and antioxidants. Participants will be followed for HIV-related outcomes for up to four years. The results from this observational study may help to guide the design of more effective interventions of antioxidant supplementation in the era of PI's.